13-20462782-A-G

Variant names:

• chr13-20462782-A-G
• rs9509234
• NM_015974.3:c.277-23028T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015974.3(CRYL1):​c.277-23028T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 151,292 control chromosomes in the GnomAD database, including 32,177 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (32177 hom., cov: 27)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 4 publications found

Genes affected

CRYL1 (HGNC:18246): (crystallin lambda 1) The uronate cycle functions as an alternative glucose metabolic pathway, accounting for about 5% of daily glucose catabolism. The product of this gene catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in the uronate cycle. The enzyme requires NAD(H) as a coenzyme, and is inhibited by inorganic phosphate. A similar gene in the rabbit is thought to serve a structural role in the lens of the eye. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYL1	NM_015974.3	c.277-23028T>C		intron_variant	Intron 3 of 7	ENST00000298248.12	NP_057058.2
CRYL1	NM_001363647.2	c.276+26588T>C		intron_variant	Intron 3 of 6		NP_001350576.1
CRYL1	XM_005266416.6	c.277-23028T>C		intron_variant	Intron 3 of 5		XP_005266473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYL1	ENST00000298248.12	c.277-23028T>C		intron_variant	Intron 3 of 7	1	NM_015974.3	ENSP00000298248.7

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92200 AN: 151174 Hom.: 32179 Cov.: 27

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.657

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.823

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.648

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.609 AC: 92210 AN: 151292 Hom.: 32177 Cov.: 27 AF XY: 0.612 AC XY: 45189 AN XY: 73862

African (AFR) AF: 0.247 AC: 10148 AN: 41138

American (AMR) AF: 0.638 AC: 9703 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.823 AC: 2853 AN: 3468

East Asian (EAS) AF: 0.720 AC: 3688 AN: 5120

South Asian (SAS) AF: 0.820 AC: 3909 AN: 4768

European-Finnish (FIN) AF: 0.702 AC: 7331 AN: 10448

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52423 AN: 67844

Other (OTH) AF: 0.643 AC: 1351 AN: 2100

Alfa AF: 0.716 Hom.: 51614

Bravo AF: 0.586

Asia WGS AF: 0.702 AC: 2440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.5
DANN	Benign	0.59
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9509234; hg19: chr13-21036921;